ArticleThe Journal of biological chemistry2015
The Interaction of Heparin Tetrasaccharides with Chemokine CCL5 Is Modulated by Sulfation Pattern and pH.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
- Benchmark of Available Explicit Solvent Models in CHARMM36m to Characterize Glycosaminoglycans.The journal of physical chemistry. B · 2025Article
- Applications of Surface Plasmon Resonance in Heparan Sulfate Interactome Research.Biomedicines · 2025Review
- A Single-Domain VNAR Nanobody Binds with High-Affinity and Selectivity to the Heparin Pentasaccharide Fondaparinux.International journal of molecular sciences · 2025Article
- Assessing Genetic Algorithm-Based Docking Protocols for Prediction of Heparin Oligosaccharide Binding Geometries onto Proteins.Biomolecules · 2023Article
- Solvent Model Benchmark for Molecular Dynamics of Glycosaminoglycans.Journal of chemical information and modeling · 2023Article
- Heparin Mimetics and Their Impact on Extracellular Matrix Protein Assemblies.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Transport of the Proinflammatory Chemokines C-C Motif Chemokine Ligand 2 (MCP-1) and C-C Motif Chemokine Ligand 5 (RANTES) across the Intact Mouse Blood-Brain Barrier Is Inhibited by Heparin and Eprodisate and Increased with Systemic Inflammation.The Journal of pharmacology and experimental therapeutics · 2023Article
- Heparan sulfates and heparan sulfate binding proteins in sepsis.Frontiers in molecular biosciences · 2023Review
- Structure and Dynamics of Human Chemokine CCL16-Implications for Biological Activity.Biomolecules · 2022Article
- Review
- Molecular dynamics simulations to understand glycosaminoglycan interactions in the free- and protein-bound states.Current opinion in structural biology · 2022Review
- Review
- From Cancer to COVID-19: A Perspective on Targeting Heparan Sulfate-Protein Interactions.Chemical record (New York, N.Y.) · 2021Review
- Discovery of rare sulfatedChemical science · 2021Article
- N-terminal Backbone Pairing Shifts in CCL5-International journal of molecular sciences · 2020Article
- Online Capillary Zone Electrophoresis Negative Electron Transfer Dissociation Tandem Mass Spectrometry of Glycosaminoglycan Mixtures.International journal of mass spectrometry · 2019Article
- Soluble syndecan-3 binds chemokines, reduces leukocyte migration in vitro and ameliorates disease severity in models of rheumatoid arthritis.Arthritis research & therapy · 2019Article
- Protein Interaction with Charged Macromolecules: From Model Polymers to Unfolded Proteins and Post-Translational Modifications.International journal of molecular sciences · 2019Review
- Cross-Species Analysis of Glycosaminoglycan Binding Proteins Reveals Some Animal Models Are "More Equal" than Others.Molecules (Basel, Switzerland) · 2019Review
- Investigation of electrospray for a capillary electrophoresis-mass spectrometry interface in reverse polarity and negative ion mode.European journal of mass spectrometry (Chichester, England) · 2019Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
Interactions between chemokines such as CCL5 and glycosaminoglycans (GAGs) are essential for creating haptotactic gradients to guide the migration of leukocytes into inflammatory sites, and the GAGs that interact with CCL5 with the highest affinity are heparan sulfates/heparin. The interaction between CCL5 and its receptor on monocytes, CCR1, is mediated through residues Arg-17 and -47 in CCL5, which overlap with the GAG-binding (44)RKNR(47) "BBXB" motifs. Here we report that heparin and tetrasaccharide fragments of heparin are able to inhibit CCL5-CCR1 binding, with IC50 values showing strong dependence on the pattern and extent of sulfation. Modeling of the CCL5-tetrasaccharide complexes suggested that interactions between specific sulfate and carboxylate groups of heparin and residues Arg-17 and -47 of the protein are essential for strong inhibition; tetrasaccharides lacking the specific sulfation pattern were found to preferentially bind CCL5 in positions less favorable for inhibition of the interaction with CCR1. Simulations of a 12-mer heparin fragment bound to CCL5 indicated that the oligosaccharide preferred to interact simultaneously with both (44)RKNR(47) motifs in the CCL5 homodimer and engaged residues Arg-47 and -17 from both chains. Direct engagement of these residues by the longer heparin oligosaccharide provides a rationalization for its effectiveness as an inhibitor of CCL5-CCR1 interaction. In this mode, histidine (His-23) may contribute to CCL5-GAG interactions when the pH drops just below neutral, as occurs during inflammation. Additionally, an examination of the contribution of pH to modulating CCL5-heparin interactions suggested a need for careful interpretation of experimental results when experiments are performed under non-physiological conditions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.